Part C, Division 5 of the Food and Drug Regulations "Drugs for Clinical Trials Involving Human Subjects" (GUI-0100): Labelling and records

On this page

1. Labelling
2. Records

Labelling

Interpretation

As defined in section 2 of the Food and Drugs Act, a label includes any legend, word or mark attached to, included in, belonging to or accompanying any food, drug, cosmetic, device or package. A package includes anything in which any food, drug, cosmetic or device is wholly or partly contained, placed or packed.

The sponsor is responsible for ensuring that the labelling of a clinical trial drug meets the requirements of section C.05.011 of Part C, Division 5 of the Regulations.

The required information outlined in this section (see box above) must be attached to, included with, or accompany each container of the drug product, and be available in both English and French.

The definition of a label permits that the required information may accompany the drug (primary container, secondary container, package inserts, etc.).

As long as a label provides all of the required information in both official languages, it would be considered to have met the requirements of section C.05.011 of the Regulations. However, traceability to the manufacturing lot should be maintained on the label immediately attached to the investigational drug (i.e. primary container) such that its identity can be determined, and, if necessary, which unit was dispensed to each participant.

Adequate labelling of a drug used in a clinical trial is essential to ensure traceability of the drug, through the use of identifying information and lot numbers, to ensure that it is dispensed to the correct clinical trial participant, and to ensure it is stored in the proper conditions, including temperature and has not expired. The labelling must comply with regulatory requirements of section C.05.011 and be coded in a manner that protects the blinding, if applicable (ICH E6, 3.15.2(a)).

It would be up to the sponsor to determine how to comply with the labelling requirements set out in this provision, provided that the system in place is validated, traceable, and does not compromise patient safety or product quality. Proper rationale and justification should be used.

For additional information on labelling, please refer to section 8.7 of Guidance document – Annex 13 to the current edition of the GMP guidelines: Drugs used in clinical trials (GUI-0036).

Clinical trial drug lot numbers

The purpose of having a lot number on a drug label is to ensure traceability back to the manufacturer's records, in the event a problem with the drug is identified or a recall is necessary. For blinded clinical trials the sponsor must ensure that labeling information does not compromise the blinding. Labeling of a clinical trial drug with a manufacturer's lot number may compromise a blinded clinical trial.

Identifiers other than a "lot" or "(L)" number (for example a batch number, a kit number or a bar code) may be considered compliant with section C.05.011, provided traceability is maintained. Where a bar code is included as the identifier on the label, the code on the drug label should readily link to information (for example lot number and expiration date) through a validated computerized system. During an inspection, Health Canada may verify that there is a system of traceability in place to ensure patient safety and that the computerized system, if applicable, is fully validated (refer to section 5.12 Records).

Clinical trial drug expiry dates

During an inspection, Health Canada may verify that the clinical trial drug has a valid expiration date. The valid expiration date assures that the drug meets the standards for potency, purity and physical characteristics.

If stability studies to support expiry dating for a clinical trial drug are still ongoing at the time of labelling, the following may be considered acceptable in lieu of an expiration date:

• a re-test date on the label if the sponsor has data to support the extended shelf-life of the drug, and
• a manufacturing date is listed on the label, as long as the clinical trial site where the drug is dispensed has a document from the sponsor documenting the shelf-life of the drug. The sponsor must have data to support the shelf-life of the drug. As an example, this principle would apply to radiopharmaceuticals.

The above process should be documented; procedures and quality control systems should be in place and in accordance with the approved CTA. It should also be performed in accordance with GMP principles and specific SOPs. This additional labelling information should be properly documented in both the trial documentation and in the packaging records.

In the cases where a drug product requires reconstitution or further preparation prior to being administered to a participant, the sponsor is responsible for demonstrating that the drug used at the clinical trial site meets all of the requirements of section C.05.011. The reconstitution or preparation of a clinical trial drug should be done in accordance with the clinical trial protocol and be documented. It is recommended that the label for any new packaging of the drug carry an expiration date. The information on the reconstitution or preparation of the drug, and the required storage conditions should be included in accompanying documentation.

The sponsor must be able to demonstrate, through adequate data, that a clinical trial drug maintains its characteristics of potency, quality and safety during its period of use.

Refer to section 8.7 of Guidance document – Annex 13 to the current edition of the GMP guidelines: Drugs used in clinical trials (GUI-0036)for additional guidance.

Labels of marketed drugs used as comparators

It is acceptable for a marketed drug used in a clinical trial as comparator (refer to Glossary (terms) for definition of comparator), to be labelled in accordance with its marketing authorization (NOC/DIN), including all relevant sections of the Food and Drugs Act and its associated regulations, provided that the labelling on the marketed drug is appropriate for the trial. The requirements of section C.05.011 would not apply in this case.

However, a marketed comparator drug used off-label must comply with the requirements of section C.05.011, unless it was not considered to be investigational in the context of the particular clinical trial, based on the assessment of the application. For additional information, refer to the Notice to stakeholders: Statement on the investigational use of marketed drugs in clinical trials. For blinded clinical trials, the sponsor should ensure that the labelling does not compromise the blinding.

An example inspection observation typically cited under this section of the Regulations includes:

• The label of the drug did not contain the required information

Records

Interpretation

As per subsection C.05.012(4), the sponsor shall maintain all records referred to in this Division for a period of 15 years. Sponsors may also be required to maintain records under provincial law, institutional policies, and contractual agreements with QIs, REBs or others. Where it is not possible to comply with both sets of requirements, the federal Regulations would govern and the records must be maintained for 15 years.

Part C, Division 5 record retention requirements also apply to clinical trials using drugs that will never be marketed regardless of the trial data's statistical significance.

Therefore, clinical trial records created and/or used during the conduct of a statistically negative trial must be retained according to the regulatory requirements as outlined in this document and in the Regulations.

All clinical trial information should be recorded, handled and stored in a way that allows its accurate reporting, interpretation and verification. This ICH GCP principle applies to all records referenced in this guidance document, irrespective of the type of media used (ICH E6, Principles 9.4 and 9.5).

All clinical trial records shall be made available for Health Canada inspectors carrying out their duties. Clinical trial participants grant Health Canada inspectors direct access to their original medical records by signing the ICF, which should include a statement to this effect as per section 2.8.10 (o) of ICH E6. A unique identifier is assigned by the QI to each trial participant, to protect their identity when the QI reports AEs and/or other trial related data (ICH E6, trial participant identification code, Glossary).

Roles and responsibilities for records retention (sponsors, QIs and REBs)

Many parties usually share the responsibilities of record retention through delegation by the sponsor. It is however the ultimate responsibility of the sponsor to ensure that all parties involved in the conduct of the trial are in compliance with record retention requirements.

Sponsor

Part C, Division 5 of the Regulations clearly establishes that the sponsor who submits the CTA is the party to whom an authorization to sell or import a drug for use in a clinical trial is issued. The sponsor of a clinical trial is ultimately responsible for maintaining all records for the required record retention period.

• As the sponsor bears responsibility for study records, it is recommended that the sponsor clarify with the QI at the outset of the trial what documents are defined as source and how they are to be maintained.
• Sponsors may delegate record retention to third parties (for example QIs, service providers, laboratories, and others). As the responsible party for the conduct of a clinical trial, the sponsor should relay their expectations to third parties and expect due diligence from all involved in the management of clinical trial records. As such, written agreements with these third parties should be secured by sponsors, prior to the commencement of the trial to ensure full compliance with the regulatory requirements with respect to records.
• Written procedures and training of personnel in their implementation should be documented to demonstrate that the maintenance and retention of records was conducted correctly and consistently. The procedures may be trial- or site-specific and be provided by the sponsor or the third party that was delegated the responsibility.
• In situations where a sponsor undergoes a change of ownership, the record retention responsibility remains with the sponsor who initially submitted the CTA, unless a written agreement is otherwise secured with the new owner. Furthermore, before the clinical trial begins, the sponsor should have a documented procedure for record retention continuity that outlines the measures to be taken in the event that the sponsor ceases to exist.
• Records should be identifiable and version controlled (when appropriate) and should include authors, reviewers and approvers as appropriate, along with date and signature (electronic or physical), where necessary (ICH E6, C.2.1).
• In order to fulfil their responsibilities in the conduct of the trial, the sponsor and QI may need access to or copies of one another's relevant essential records before and during the conduct of the trial. At the end of the trial, each party should retain their essential records (ICH E6, 2.12.11 and 3.16.3(a)).
• The sponsor should not have exclusive control of data captured in data acquisition tools in order to prevent undetectable changes (ICH 3.16.1(l)).

For activities that are transferred or delegated to service providers by the sponsor or QI/institution, respectively, arrangements should be made for the access and management of the essential records throughout the trial and for their retention following completion of the trial (ICH E6, C.2.2). The sponsor and QI/institution should retain the essential records in a way that ensures that they remain complete, readable and readily available and are directly accessible (ICH E6, C.2.6).

Qualified investigator

A QI is responsible for the proper conduct of the clinical trial at their site. It should be noted that an independent QI, initiating a clinical trial under their own sponsorship, is responsible for all aspects of that trial, both as a QI and as a sponsor.

• The QI should retain the essential records for the required retention period in accordance with applicable regulatory requirements or until the sponsor informs the QI that these records are no longer needed, whichever is the longest. The QI should take measures to ensure availability, accessibility and readability and to prevent unauthorised access and accidental or premature destruction of these records (see Appendix C) (ICH E6 2.12.12).
  • Sites that neither screen nor enrol any participants in a given clinical trial and that have not been delegated the responsibility of record retention by the sponsor do not need to retain clinical trial records in accordance with Part C, Division 5. Since the sponsor of a clinical trial is responsible for maintaining all records, the QI should consult the sponsor to confirm record retention requirements prior to destroying any record.
  • Clinical trial sites with screen failures but no participants enrolled in a given clinical trial should retain all records, including ones pertaining to screen failures for the entire record retention period as per Part C, Division 5. All source documents should also be retained for the entire record retention period even if a participant has withdrawn from the clinical trial
• Written agreements describing the procedures for records retention in accordance with the Regulations should be in place between all parties concerned:
  • For example, QIs conducting clinical trials within a hospital or a medical clinic should secure a written agreement (for example contract, policy, SOP), if applicable, with the institution to ensure that hospital records and/or medical charts of clinical trial participants are retained according to the federal Regulations as these prevail over provincial laws and regulations when there is a conflict
  • Agreements should also outline the conditions of record retention, such as the location of records, as well as the procedure to be followed to ensure record retention within the 15-year period in the event that a company ceases to exist or QI ceases her/his affiliation with their institution, for various reasons (for example closure of practice or retirement, new position elsewhere, or death)
• The QI may delegate record-related tasks to other parties such as the institution's pharmacy, a local laboratory or a radiological clinic, with the sponsor's agreement:
  • Prior to the commencement of the clinical trial, the delegated tasks should be documented, signed and dated by the QI and the party to whom the functions are delegated. Documentation of delegation should be proportionate to the significance of the trial-related activities (ICH E6, 2.3.3). The delegation may be amended if necessary during the course of the clinical trial
  • The extent of the delegation, including the retention of the records created by the other party, should be clearly stated
  • Tasks that are not delegated remain under the direct responsibility of the QI or the sponsor, depending on the written agreement secured between these two (2) parties. However, QIs always remain responsible to oversee the delegated tasks because they are responsible for the trial at their site
• The QI/institution should maintain adequate source records that include pertinent observations on each of the site's trial participants under their responsibility. Source record(s) should be attributable, legible, contemporaneous, original, accurate, and complete (ALCOAC). Changes to source records should be traceable, should not obscure the original entry, and should be explained if necessary (for example via an audit trail). The QI should define what is considered to be a source record(s), the methods of data capture and their location prior to starting the trial and should update this definition when needed. Unnecessary transcription steps between the source record and the data acquisition tool should be avoided (ICH E6, 2.12.2).
• Section 2.12.5 of ICH E6 states that the QI should ensure the accuracy, completeness, legibility, and timeliness of the data reported to the sponsor in the data acquisition tools completed by the QI site (for example CRFs) and in any other required reports (for example SAE reports). The QI should review and endorse the reported data at important milestones agreed upon with the sponsor (for example interim analysis) (see section 3.16.1(o)). Furthermore, section 2.12.6 of ICH E6 states that data reported to the sponsor should be consistent with the source records or the discrepancies explained. Changes or corrections in the reported data should be traceable, should be explained (if necessary) and should not obscure the original entry.
• In addition, the QI should be provided with timely access to data by the sponsor (see section 3.16.1(k)) and be responsible for the timely review of data, including relevant data from external sources that can have an impact on, for example, participant eligibility, treatment or safety (for example, central laboratory data, centrally read imaging data, other institution's records and, if appropriate, electronic patient-reported outcome (ePRO) data). The protocol may provide exceptions for access, for instance, to protect blinding (ICH E6, 2.12.3). Furthermore, the investigator should ensure that data acquisition tools and other systems deployed by the sponsor are used as specified in the protocol or trial-related instructions (ICH E6, 2.12.4).

Types of records

Different types of records are created and are to be retained before, during and after the conduct of a clinical trial, in accordance with section C.05.012 of the Regulations and appendix C "Essential Records for the Conduct of a Clinical Trial" of ICH E6.

Essential records

Documents and data (and relevant metadata) in any format, associated with a clinical trials that facilitate the ongoing management of the trial and collectively allow the evaluation of the methods used, factors affecting a trial and the actions taken during the trial conduct to determine the reliability of the trial results produced and the verification that the trial was conducted in accordance with GCP and applicable regulatory requirements (see Appendix C)(ICH E6, glossary).

These include, but are not limited to:

• investigator's brochure (including records respecting each change)
• serious adverse event (SAE) and serious adverse drug reaction (SADR) reports that have occurred inside or outside Canada
• chemistry and manufacturing information
• records respecting the enrolment of clinical trial participants
• records respecting the shipment, receipt, disposition, return and destruction of the drug
• signed and dated QIU forms (Phase I-IV trials)
• protocols and protocol amendments
• REB approved ICF(s)
• signed and dated REB attestations
• standard operating procedures (SOPs)
• site personnel training records
• source records

Source records

A type of essential record that consist of original documents or data (includes relevant metadata) or certified copies of the original documents or data, irrespective of the media used (ICH E6, glossary).

These include, but are not limited to:

• signed and dated ICFs
• hospital records
• clinical site and physician office medical charts
• laboratory records
• medical instrument records, including wearables
• X-rays
• participant diaries and medical records
• appointment/scheduling records
• AEs and ADRs records
• pharmacy dispensing records
• drug accountability records

It is acceptable for essential and/or source records to be transferred to secondary media (see "Transfer of records to secondary medium" section below).

The assessment of whether a record is essential and has to be retained should take into account the criteria outlined in ICH E6 Section C.3 (Essentiality of Trial Records).

A method is expected to be in place to identify those data elements requiring source documentation, and sites can then declare the type of source records (for example chart-based, electronic record, a combination).

Only specific and unique records that belong solely to the sponsor, the REB, the QI or other entities, must be kept at the conclusion or termination of a trial. Retention of copies of original documents is not a requirement.

The QI should have access to and the ability to maintain the essential records generated by the QI before and during the conduct of the trial and retain them in accordance with applicable regulatory requirements (ICH E6, C.1.3).

In order to allow traceability of all source data, any source records should be signed and dated by the person collecting, recording, revieing and/or assessing the information or data.

Signing and dating a source record as evidence that it was reviewed is a common practice often supported by the site internal policies.

This practice is also recommended by Health Canada, although alternative verification methods, consistent with the principles of ICH E6, may also be acceptable (for example proper documentation in the progress notes).

In situations where original source records cannot be retained for the 15-year record retention period due to their deterioration in uncontrolled environment conditions (for example thermal paper used for electrocardiograms), certified copies can be acceptable (see "Transfer of records to secondary medium" section below).

A certified copy is a copy (irrespective of the media used) of the original record that has been verified (for example by a dated signature or by generation through a validated process) to have the same information as the original, including relevant metadata, where applicable (ICH E6, glossary).

Refer to appendix C of ICH E6 for a more detailed list of essential and source documents.

Electronic records

Electronic records may be generated during clinical trials. They consist of any piece of information that is created, modified, retrieved, and/or transmitted during the conduct of a clinical trial.

These may include, but are not limited to:

• electronic case report forms (eCRFs) including electronic signatures
• electronic participant diaries
• other instruments provided to the QI or participants to record trial data

Key concepts include:

• Electronic records should be maintained and retained in accordance with section C.05.012 of the Regulations.
• Systems and processes that aid in data capture, management and analyses, as well as those that help ensure the quality of the information generated from the trial, should be fit for purpose, should capture the data required by the protocol and should be implemented in a way that is proportionate to the risks to participants and the importance of acquired data (ICH E6, Principle 9.2).
• Computerised systems used in clinical trials should be fit for purpose (for example, through risk-based validation, if appropriate), and factors critical to their quality should be addressed in their design or adaptation for clinical trial purposes to ensure the integrity of relevant trial data (ICH E6, Principle 9.3).
• The validation of an electronic system is performed to confirm that the system's specifications meet the goals and requirements for the clinical trial in a consistent manner. These include, but are not limited to, completeness and accuracy of recorded information as well as reliability of the system. Therefore, any electronic system used to capture, process, manage and/or archive clinical trial information should be adequately validated and evidence of validation should be kept for the required record retention period and should be readily available for inspection by Health Canada's Inspectors.
• The approach for validation should be based on a risk assessment that considers the intended use of the system; the purpose and importance of the data/record that are collected/generated, maintained and retained in the system and the potential of the system to affect the well-being, rights and safety of trial participants and reliability of trial results (ICH E6, Computerised Systems Validation in glossary and 4.3.4).
• As part of the validation process for electronic systems, documentation of the system design specifications and a validation plan based on those should be developed.
• The validation plan should include:
  • objectives and scope
  • nature of and time at which validation activities should be performed
  • delegated personnel for the conduct of the validation
  • security measures
  • main features of the system, including the mode of interaction with other systems and procedures
• Detailed documented procedures for validation activities should be developed and followed at all times to ensure consistency in the performance of the tasks. The SOPs should cover system design, setup, installation, and use. The SOPs should describe :
  • system validation and functionality testing
  • data collection and handling
  • system requirement and maintenance
  • system security measures
  • change control
  • data backup, recovery, contingency planning, and decommissioning.
• The responsibilities of the sponsor, QI, and other parties with respect to the use of these computerized systems should be clear, and the users should be provided with training in their use (ICH E6,4.3.1 and 4.3.2).
• The validation results should provide a clear indication that the system can be used as created. As such, a validation report, including detailed test results and an assessment of the results demonstrating that the system has met the specifications, should be produced for each validation test and allow traceability to the delegated person who conducted the activity.
• Any modifications or additions made to the electronic system (for example software upgrades or migration of data) can impact its intended functions by altering the quality of validated applications and the system itself. This may affect the integrity of the electronic information and the reliability of the system. Therefore, adequate documented assessment and approval of changes to hardware or software during the course of the clinical trial are required. The impact of such a change should be evaluated and documented, and partial validation of some components of the electronic system may be required.
• The electronic system should allow for the retrieval of the records, the generation of complete and accurate paper copies of the electronic source data as well as provide audit trails for the entire 15-year record retention period.
• Records created, maintained and processed by outsourced systems (i.e. cloud computing) are subject to the same requirements as the data/records generated by company owned systems.
• For electronic medical records system (for example hospital-based systems) not under the responsibility of the sponsor, an alternate method to validation could be considered (for example printing).
• The responsibilities of sponsor for data handling should ensure:
  • the integrity and confidentiality of data generated and managed (ICH E6, 3.16.1(a))
  • data acquisition tools are fit for purpose and designed to capture the information required by the protocol. They should be validated and ready for use prior to their required use in the trial (ICH E6, 3.16.1(d))
  • documented processes are implemented to ensure the data integrity for the full data life cycle (see section 4.2 of ICH E6) (ICH E6, 3.16.1(e))
  • trial data are protected from unauthorized access, disclosure, dissemination or alteration and from inappropriate destruction or accidental loss (ICH E6, 3.16.1(v))
  • records of the important computerized systems used in a clinical trial such as the use, functionality, interfaces and validation status of each computerized system, and who is responsible for its management should be described. The record should also include a description of implemented access controls and internal and external security measures (ICH E6, 3.16.1(x)(i))
  • the requirements for computerized systems (for example, requirements for validation, audit trails, user management, backup, disaster recovery and IT security) are addressed and implemented and that documented procedures and adequate training are in place to ensure the correct development, maintenance and use of computerized systems in clinical trials (see section 4 of ICH E6(R3)). These requirements should be proportionate to the importance of the computerized system and the data or activities they are expected to process (ICH E6, 3.16.1(x)(ii))
• Health Canada expects that sponsors take into consideration the following factors as part of the risk assessment of a computerised system and its associated validation, but not limited to:
  • type of research (for example commercial vs. non-commercial)
  • purpose of the clinical trial (for example research for publication vs. drug submission for marketing authorization)
  • status of the drug (for example market authorized product vs. investigational drug)
  • safety profile / history of use of the drug

  In addition, the sponsor should periodically review the risk control measures identified in their assessment to ascertain whether the implemented systems remain effective and relevant, taking into account experience and emerging knowledge (ICH E6, 3.10.1 and 4.3.4).

For additional information on computerized system validation and electronic records, refer to:

• Annex 11 to the good manufacturing practices guide: Computerized Systems: GUI-0050
• PIC/S Guidance: Good Practices for Computerised Systems in Regulated "GXP" Environments
• the U.S. Code of Federal Regulations Title 21 Part 11 – Electronic Records; Electronic Signatures
• the U.S. Food and Drug Administration (FDA) Guidance for Industry: Computerized Systems Used in Clinical Investigations
• the Medicines and Healthcare products Regulatory Authority (MHRA) GXP Data Integrity Guidance and Definitions (PDF format)
• World Health Organization (WHO) Annex 5 Guidance on Good Data and Record Management Practices (PDF format)
• the standard Electronic Records as Documentary Evidence, CAN/CGSB-72.34-2024 (PDF format) developed by the Canadian General Standard Board (CGSB).

Pharmacy records

Pharmacy records should be retained as either part of the participant-specific source record or the medical or hospital chart.

These records include, but are not limited to:

• clinical trial drug prescriptions
• calculations for clinical trial drug dispensing
• drug accountability records
• clinical trial drug storage temperature logs

Drug accountability records

Drug accountability records should include the following information on the drug, but not limited to:

• date of arrival on site
• quantity received
• identification (batch/lot number)
• expiration date
• quantity dispensed, on what date and to whom
• quantity returned by participants, on what date
• quantity and date of destruction or return to sponsor

In order to ensure that participants received the product(s) according to their randomization, QIs should maintain records.

The QI and/or a pharmacist or other appropriate individual should maintain records of the product's delivery, the inventory, the use by each participant (including documenting that the participants were provided the doses specified by the protocol) and the return to the sponsor and destruction or alternative disposition of unused product(s). These records should include dates, quantities, batch/serial numbers, expiration dates (if applicable) and the unique code numbers assigned to the investigational product(s) and trial participants (ICH E6, 2.10 .4).

Drug accountability records are required for:

• drugs that are the subject of the clinical trial, and do not have market authorization
• drugs that are the subject of the clinical trial, have market authorization, but are used off-label
• comparator drug, if it does not have market authorization
• comparator drug, if it has market authorization, but its labelling was changed (for example for blinding purposes)
• comparator drug, if it has market authorization, but is used off-label (unless it was not considered to be investigational in the context of the particular clinical trial, based on the assessment of the application)

Drug accountability records are not required for:

• drugs that are the subject of a Phase IV clinical trial
• comparator drug, if it has market authorization, is used on-label, and hasn't been altered in any manner
• rescue or concomitant medications, authorized for sale in Canada, that may be used on or off-label but are not the subject of the clinical trial (for example they are used as supportive medications for known clinical applications)

For example, marketed drugs which are commercially available, for which no CTA has been filed (Phase IV), should be managed as commercial drugs and good practice guidelines for pharmacies followed.

Trial-specific drug accountability logs are required only for drugs specifically labelled as clinical trial supply (i.e. drugs included on NOL).

For additional information on the off-label use of a drug that is authorized for sale in Canada, refer to the Notice to stakeholders: Statement on the investigational use of marketed drugs in clinical trials.

Laboratory records

The retention of laboratory records allows review and confirmation of the diagnoses and results/reports as well as appropriate further testing, if needed, for the protection and well-being of clinical trial participants.

These records include, but are not limited to:

• normal values and/or ranges for test(s) included in the protocol
• laboratory certification and/or accreditation
• established quality control and/or external quality assessment
• laboratory results/reports
• X-ray films, digital images, microfilms and compact disks

Medical instrument records

In the course of a clinical trial, measurement and laboratory equipment, scientific instruments and other pieces of equipment are generally used. Using a risk-based approach, the sponsor should identify critical equipment used in a study and specifications for that equipment (refer to section C.05.010(c) Equipment and Calibration).

• All service, maintenance, cleaning and calibration records, as well as the product manual for a critical piece of equipment used in the clinical trial, should be retained for the 15-year record retention period. This would include for example certificates, calibration data, and records of faults, breakdowns and misuse of the equipment.
• The manual calibration of certain pieces of equipment or instruments (for example body weight scales) does not generate a certificate or a print-out of the calibration data to demonstrate that the calibration was indeed performed and successful. In those circumstances, the QI should retain the calibration procedure and a log stating the following information:
  • dates of calibration
  • device details (type, supplier, and purchase date)
  • person responsible for the instrument
  • person who performed calibrations

  Approved specifications for calibration should also be documented and a record of the actual calibration results kept.

• Certain pieces of equipment or instruments may require frequent automated calibration and consequently generate considerable amounts of print-outs. In these instances, a log should be kept with all of the information listed under the bullet point above; except it should include the name of the person who assessed the calibration data and certified that calibration was successful, instead of the person who calibrated the instrument.
• The manufacturer's warranty cannot replace calibration/maintenance records as equipment calibration assures that equipment works within specifications.

Financial records

Records pertaining to financial details of the clinical trial include, but are not limited to:

• any subject compensation records
• financial agreements between parties (ICH E6,3.5 and C.3.2)
• insurance statements (ICH E6, 3.14.1)

Financial details related to clinical trial records are at the sponsor's discretion and outside of Health Canada scope.

Refer to Appendix C of ICH E6 for more information on this type of record.

Research ethics boards (REBs) records

Records relevant to a clinical trial that pertain to the roles and responsibilities of the REB should be retained for 15 years in accordance with Part C, Division 5 of the Regulations.

These records could include, but are not limited to:

• REB membership including roles and responsibilities (for example chair, ethics, community representative)
• qualifications of REB members
• REB decisions (for example approvals, denials, required modifications, orders to stop clinical trials, etc.)
• communications with sponsors and Qis

The REB should retain all relevant records in accordance with applicable regulatory requirements and make them available upon request from the regulatory authority(ies) (ICH E6 1.5.1).

The REB may be asked by QIs, sponsors or regulatory authorities to provide its documented procedures and membership lists (ICH E6 1.5.2).

Transfer of records to secondary medium

The transfer of essential records from their original medium to a secondary one may be acceptable if the conditions described in this section are fulfilled.

Transfer

The transfer process should be validated and documented in appropriate procedures, and should ensure that:

• measures are in place to verify that the transfer is accurate and done by appropriately trained individuals (for example attestation or certification of copies by a person not involved in the transfer)
• corrections to the original data can be clearly captured in the secondary medium
• process follows existing standards when possible (i.e. Canadian General Standard Board)
• the secondary medium allows the successful retrieval and use of the records for the entire 15-year record retention period

Where records are copied off-site, a contract signed by the sponsor/QI/institution and the service provider must detail specific requirements such as those for transport to that site, copy quality, storage conditions, and, where relevant, destruction of original documents.

Electronic or other system

The format and system where documents are retained should also be validated for its intended use.

Features should include the following, but not be limited to:

• design to ensure the tracing of any alterations and updates, if permitted, such as source, date and content (i.e. audit trail)
• back-ups at regular intervals
• security measures in place and documented to protect against data corruption, whether through accidental deletion, equipment failures, material deterioration, or a variety of other hardware and software problems
• controlled access to appropriate individuals (for example through use of passwords)
• plan in place for future accessibility (in light of changes over time in technology, personnel, or third-party contractors)
• location of records that permits immediate access to records for inspection

Destruction of original records

The destruction of original paper records following their transfer to a secondary medium may be acceptable with the principles described in this section in place.

In addition, the process to describe the destruction of the original paper records should be documented in appropriate procedures. Considerations should be given to additional requirements that may apply to the destruction of personal/confidential information.

Other considerations

Other requirements may apply to the transfer, storage and destruction of records, including:

• provincial (for example medical records)
• institutional
• legal requirements

It is considered acceptable, for example, to scan records in an electronic format and store them on specific software or networks as well as on other devices such as flash drives (for example USB keys). That being said, all requirements stated in this guidance should be met when using any of these storage methods. While only one copy of each record in archive must be retained, whether in hardcopy or electronic format, records from their original medium (for example hardcopies) should be kept for as long as they are needed. When a copy is used to replace an original record (for example source records, CRF), the copy should fulfil the requirements for certified copies as defined above (see ICH E6, glossary).

The above conditions apply to transfers of essential records from an original to a secondary medium performed by all parties involved in the conduct of a clinical trial.

For more information with regards to the transfer of essential records to a secondary medium, refer to the CGSB standard: Electronic records as documentary evidence,CAN/SBCGSB-72.34- 20254.

Record retention period

The retention period for all records created and/or used during the conduct of a clinical trial is 15 years in accordance with subsection C.05.012(4) of the Regulations. This period of time will allow for subject follow-up throughout the subsequent stages of drug development, assessment, marketing, as well as provide the ability to assess the impact on the next generation.

Although the retention period of records starts on the date the record is created, sponsors may choose to "start the clock" for retention of all study records upon completion or termination of the trial to simplify the process.

Location of records

Often, third parties (such as QIs, REBs, Service Providers) retain originals of specific and unique records created by them. Nevertheless, due to their nature, specific records may be retained by more than one party. It should be noted that it is not a requirement for a party to retain multiple and identical copies of an original record. Third parties should consult the sponsor prior to destroying any record.

The QIs should keep the sponsor informed of the name of the person responsible for maintaining the essential records during the retention period; for example, when the QIs site closes or a QIs leaves the site (ICH E6, 2.12.13).

All records should be kept in a secure location prior to, throughout and after the conduct of the clinical trial. To maintain the integrity of all records, their location should assure protection from possible damage (for example water or fire damage) and from a possible breach in confidentiality for the entire record retention period. As such, access to the records should be restricted to authorized personnel that are adequately trained in the handling and management of clinical trial records according to an established documented procedure.

The sponsor and QI should maintain a record of where essential records are located, including source records. The storage system(s) used during the trial and for archiving (irrespective of the type of media used) should provide for appropriate identification, version history, search and retrieval of trial records (ICH E6, C.2.4).

It should be noted that specific timelines for the provision of clinical trial information to Health Canada are outlined in section C.05.013 of the Regulations (see section 5.13 of this document). These timelines should be taken into consideration when determining the location of the clinical trial records for the retention period.

If the records are stored in the cloud, there should be an agreement between the sponsor and the cloud provider that sets out the parties' respective responsibilities. Direct and immediate access to the records needs to be available for inspectors and provision of passwords or encryption keys to inspectors at the time of inspection.

Examples of inspection observations typically cited under this section of the Regulations include:

C.05.012(1) and C.05.012(2)

• The clinical trial records had errors and/or missing information that did not allow for complete and accurate reporting, interpretation, and verification
• The sponsor did not always record, handle and store all information for a clinical trial to ensure the data transcribed from the original documents to case reports was accurate and complete
• The sponsor did not ensure the electronic data system met the requirements for completeness, accuracy, and reliability
• The sponsor did not always maintain complete and accurate records to show the clinical trial was conducted in accordance with GCP and the Regulations

C.05.012(3)

• The sponsor did not always maintain complete and accurate records for the use of the drug in the clinical trial, as required by the Regulations
• The sponsor did not maintain all versions of the Investigator's Brochure, including the rationale for any changes and documentation supporting each change
• The sponsor did not maintain records of all adverse events occurring from the drug in or outside Canada
• The sponsor did not maintain records for shipping, receiving, disposing of, returning and/or destroying the drug
• The sponsor did not maintain records of an undertaking from the QI. This undertaking form must be signed and dated by the QI before the commencement of their responsibilities in the clinical trial
• The sponsor did not maintain copies of the protocol, informed consent form and/or any amendments to the protocol or informed consent form approved by the REB for the clinical trial site

C.05.012(4)

• The sponsor did not have provisions in place to keep all clinical trial records for a period of 15 years